Statins Prevent Vascular
Topic: Prevention/Vascular
Date Posted: 2/26/2009
Author(s): Shalev V, Chodick G, Silber H, Kokia E, Jan J, Heymann AD.Study
Question: The value of statin therapy in reduction of overall mortality in patients without coronary heart disease (CHD) is not clear. This study evaluated the effect of statin therapy in subjects with no indication of cardiovascular disease (primary prevention) and patients with known CHD (secondary prevention).
Methods: This retrospective cohort study included 229,918 (primary prevention 136,052 and secondary prevention 93,866) adult enrollees in a health maintenance organization in Israel who initiated statin treatment from 1998 through 2006. Proportion of days covered (PDC) with statins was measured by the number of dispensed statin prescriptions during the interval between the date of the first statin prescription and the end of follow-up.
Results: Mean age was 54.8 years in primary prevention and 61.5 years in secondary prevention, and 50.8% were female. Mean baseline low-density lipoprotein cholesterol (LDL-C) was 154.8 and 162.5 mg/dl in the primary and secondary prevention groups, respectively. The dominant statins used were simvastatin in 80% and atorvastatin in 8%. More frequent physician visits and higher statin efficacy were associated with a mortality risk reduction. Less than moderate statin efficacy (<31% reduction in LDL-C) was found in 35% of subjects. During a mean of 4.0 and 5.0 years of follow-up, there were 4,259 and 8,906 deaths among the primary and secondary prevention cohorts, respectively. In both cohorts, continuity of treatment with statins (PDC, ≥90%) conferred at least a 45% reduction in risk of death compared with patients with a PDC of <10%. A stronger risk reduction was calculated among patients with high LDL-C and patients initially treated with high-efficacy statins. There was no difference in incident creatine kinase >10 x upper limit of normal in those with PDC >90% compared to <10%, and small differences in liver function.
Conclusions: Better continuity of statin treatment provided an ongoing reduction in mortality among patients with and without a known history of CHD. The observed benefits from statins were greater than expected from randomized clinical trials.
Perspective: It is just this type of very large clinical observational study that was necessary to help clarify the value of statins for reducing total mortality, and whether greater LDL-C lowering is of value. This study, demonstrating at least a 45% reduction in overall mortality from statins, should help convince patients and physicians regarding long-term use and the lower is better hypothesis. But, how low is low enough, and what dose is the optimal dose, remains to be seen.
